Rapid progress in the areas of molecular virology and molecular epidemiology of human caliciviruses (HuCVs) in recent years highlights the clinical importance and worldwide distribution of HuCVs as a cause of acute gastroenteritis in humans. This renewal builds on the scientific productivity of the past and will initiate new research initiatives based on novel approaches. Our long-term goals are to seak new information about the virology, immunology and pathogenesis of HuCVs and to develop strategies to control and prevent the diseases caused by these viruses. The following four specific aims will be addressed. Specific aim 1. To define the HuCV antigenic types and develop diagnostic assays for detection and typing using type-common and type-specific antibodies. Specific aim 2. To characterize the infection status and immunity of children and adults involved in sporadic and outbreak episodes of gastroenteritis using type-common and type-specific assays against HuCVs. Specific aim 3. To characterize the molecular basis of virus-cell interaction and possible viral receptor(s) using recombinant virus-like particles (VLPs) as a probe. Specific aim 4. To characterize primate CV (PrCV) replication and attempt to cultivate HuCVs in cell culture using novel approaches learned from animal CVs.